反应详情

3-[(Piperidin-4-yl)carbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (100 mg) obtained in Example 228 is suspended in 2-butanol (5 ml), and thereto are added 2-bromothiazole (113 μl) and N,N-diisopropylethylamine (131 μl), and the mixture is heated under reflux for 24 hours. To the reaction solution are added 2-bromothiazole (57 μl) and N,N-dimethylacetamide (2 ml), and the mixture is further heated under reflux for 24 hours. To the reaction solution is poured a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with chloroform. The organic layer is washed with water and a saturated brine, and dried over sodium sulfate. The solvent is evaporated under reduced pressure, and the resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=3/1, then ethyl acetate) to give 3-[[1-(2-thiazolyl)piperidin-4-yl]-carbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide (38 mg). This product is further treated with hydrogen chloride in dioxane to give the title compound (25 mg).

1. temperaturethe mixture is heated
2. temperatureunder reflux for 24 hours
3. temperaturethe mixture is further heated
4. temperatureunder reflux for 24 hours
5. extractionthe mixture is extracted with chloroform
6. washThe organic layer is washed with water
7. dry with materiala saturated brine, and dried over sodium sulfate
8. customThe solvent is evaporated under reduced pressure
9. customthe resulting residue is purified by silica gel column chromatography (eluent